We’re now passing over to @DrGWheeler to walk us through software for adaptive designs!
Sorry, attempt 2 (@JMSWason not too experienced with adding gifs!)
In 2020 Michael Grayling @UniofNewcastle & @DrGWheeler @ucl published a review of software for #AdaptiveDesigns in clinical trials.

Lack of available software is a known barrier to using better trial designs in practice. Q: “How bad is this problem?” 1/9
Our research questions were:

1. How many articles proposing new adaptive designs included code with the paper, or a link to code available elsewhere?

2. Which adaptive design approaches and features are well supported by current software, and (importantly), which are not? 2/9
For Q1, we reviewed 4,123 articles published from 2013-2017 across 31 journals. Of these, 247 articles from 26 journals were considered eligible.

174 (70%) articles provided no code relating to the proposed method.

Figure 1 shows code provision status by journal. 3/9 Image
We found that even if journals had a compulsory code provision policy, this wasn't a guarantee that code was available.

Figure 2 shows code provision by journal policy. Of 66 publications in Statistics in Medicine, which required authors to supply code, 51 (77%) did not. 4/9 Image
129 (52%) articles stated what software was used, but 60 (47%) such articles did not make their code available. #R was by far the most popular software used (107 (91%) articles, 16 of which used R with another program, or provided code in R and another language). #Rstats 5/9 Image
For Q2, we searched software libraries to see which adaptive designs were available. Of 122 eligible records, most were for group sequential methods in phase II & III trials. Few were available for sample size adjustment, adaptive randomization, or biomarker-based methods. 6/9 Image
Finally, we looked at the quality of support around each record. Of the 122 records, 95 (78%) provided help files, but only 42 (34%) provided a detailed guide or vignette. Only 16 records (13%) contained “well annotated” code. 7/9
1. Most articles proposing adaptive designs for clinical trials don’t provide code or software;
2. Adaptive trial resources focus on group sequential methods for later phase trials;
3. Help files are often provided with code, but annotation of code is poor. 8/9
Finally, two tips for adaptive design researchers:

1. Learn some basic #R, as this is what most packages are written in. Plus, you can take an existing package and tweak that code for your own work.


Thanks for reading! #AdaptiveDesigns 9/9

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26 Feb
While platform trials are clearly more prominent in COVID-19 than they were before the pandemic, many other COVID-19 trials use adaptive features. Some examples to follow. #adaptivedesigns

The MATIS trial (NCT04581954) is a multi-arm multi-stage trial with early stopping for lack of benefit which seeks to evaluate treatments to prevent more severe disease. @JMSWason

Similarly, the RECOVERY-Respiratory Support trial (ISRCTN16912075) seeks to identify optimal respiratory support using a multi-arm multi-stage structure. More details are here:


@recovery_rs @WarwickCTU

Read 4 tweets
26 Feb
A number of COVID-19 trials use a platform structure and we will look at a few examples in the later stages of development in this thread. #adaptivedesigns
(1/6) Image
The first treatment to be shown to benefit COVID-19 patients was identified within the ACTT trial. The platform allows to stop the evaluation for benefit and lack thereof as well as adding additional treatments.


The RECOVERY trial (recoverytrial.net) is with 38,000 patients to date the largest COVID trial. This has allowed several questions to be answered including dexamethasone as an effective treatment for severe disease.
@PeterHorby @MartinLandray @RichardHaynes3 (3/6) Image
Read 6 tweets
26 Feb
Throughout this week we have made the case that adaptive designs can be useful to improve efficiency and discussed practical challenges. Two recent papers have made the case that trials that are adaptive can be particularly helpful in the of COVID-19. #adaptivedesigns (1/4)
Different types of adaptations and their utility for studies of COVID-19 treatments have been reviewed in

But the utility of adaptive designs is not limited to studies of COVID-19 treatments. They can also be useful for trials that are impacted by COVID-19 as argued here.

Read 4 tweets
25 Feb
The TAIloR trial (ISRCTN: 51069819) was a multi-arm multi-stage clinical trial that investigated the utility of different doses of telmisartan to reduce insulin resistance in HIV-positive individuals. @thomas_jaki (1/n).
The trial had one interim analysis during which doses that were deemed insufficiently promising were dropped from the study and in the study two of the initial three doses were dropped at this point. (2/n)
Due to the ability to eliminate insufficiently promising doses, fewer patients were exposed to doses that did not provide benefit to patients. (3/n)
Read 4 tweets
25 Feb
The NOTACS trial (ISRCTN: 14092678) an adaptive, multicentre, parallel group, randomised controlled trial comparing the efficacy, cost-effectiveness and safety of 2 types of oxygen therapy in patients at high risk of post-operative pulmonary complication after cardiac surgery 1/n
The trial has an embedded interim sample size re-estimation, which is a type of adaptive trial design. This is joint work by @RoyalPapworth, @MRC_BSU (inc. @SofiaSVillar1, @SarahNDawson) (2/n)
After a pre-defined number of patients have been recruited and completed follow-up, we will use the data accumulated so far to re-estimate the nuisance parameters and use these to repeat the sample size calculation. (3/n)
Read 4 tweets
24 Feb
Adaptive designs, and other innovative approaches, provide great benefits but are also more complex to run. In 2019, the Adaptive Designs Working Group started investigating what extra resource Clinical Trials Units (CTUs) might need to support #adaptivedesigns. (1/7)
Funded by the @NIHRresearch @UKCTUNetwork CTU Support Fund and led by Newcastle CTU, the “Costing Adaptive Trials (CAT)’ project set about answering this question. Step 1 was a snazzy logo. (2/7) Image
We then did a mock costing exercise. Seven CTUs agreed to cost five trial scenarios - each based on a real trial. For each, we outlined a non-adaptive and adaptive version. CTUs returned the staff resource and other costs that they’d put in a funding application. (3/7)
Read 7 tweets

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